Abstract

Disruption of cell architecture and change of energy metabolism are two traits of malignant cells. Yet, there was scant evidence that these two cancer hallmarks involved perturbations of a common signaling pathway. Enter LKB1, a kinase that is a tumor suppressor and that is an upstream activator of the adenosine monophosphate (AMP)–activated protein kinase (AMPK), a key sensor of cellular energy status. Four studies now reveal that LKB1 signals through AMPK to facilitate the formation of tight junctions and to maintain epithelial polarity. Thus, LKB1 appears to be a novel class of tumor suppressor that acts as an energy-sensing and polarity checkpoint.